The process of opsonization is one of the most important biological barriers to
controlled drug delivery. Injectable polymeric nanoparticle carriers have the ability to
revolutionize disease treatment via spatially and temporally controlled drug delivery.
However, opsonin proteins present in the blood serum quickly bind to conventional nonstealth
nanoparticles, allowing macrophages of the mononuclear phagocytic system
(MPS) to easily recognize and remove these drug delivery devices before they can
perform their designed therapeutic function. To address these limitations, several
methods have been developed to mask or camouflage nanoparticles from the MPS. Of
these methods, the most preferred is the adsorption or grafting of poly(ethylene glycol)
(PEG) to the surface of nanoparticles. Addition of PEG and PEG-containing copolymers
to the surface of nanoparticles results in an increase in the blood circulation half-life of
the particles by several orders of magnitude. This method creates a hydrophilic
protective layer around the nanoparticles that is able to repel the absorption of opsonin
proteins via steric repulsion forces, thereby blocking and delaying the first step in the
opsonization process.